Study to Evaluate Safety, Tolerability and Pharmacokinetics of CS060380 in Healthy and Elevated LDL-C Subjects

A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of Randomized, Double-Blind, Placebo-Controlled Single and Multiple Dose Escalations of CS060380 in Healthy and Elevated LDL-C Subjects

Study to Evaluate Safety, Tolerability and Pharmacokinetics of CS060380 in Healthy and Elevated LDL-C Subjects.

Study Overview

• Status: Completed
• Conditions: MASH
• Intervention / Treatment: Drug: CS060380

Detailed Description

A Phase I study Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effects of Randomised, Double-Blind, Placebo-Controlled Single and Multiple Dose Escalations of CS060380 in Healthy and Elevated LDL-C Subjects.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Xuhui Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

SAD

1. Sign and date the ICF.
2. Signing ICF age≥18 years≤55 years, male or female.
3. Weight: Male≥50kg, female≥45kg BMI: 18~28kg/m².
4. Female or male subjects must be eligible for contraception during the study.
5. Normal renal function.
6. Good general health.
7. No significant medical history, in good general health as assessed by the study during the Screening Period and no more than 28 days from the first dose.
8. Understand and comply with study procedures and limitations.

MAD

1. Sign and date the ICF.
2. Signing ICF age≥18 years≤65 years, male or female.
3. Weight: Male≥50kg, female≥45kg BMI: 18~35kg/m², including at least 25% of overweight subjects ( BMI : 25~30 kg/m² ), and at least 25% of obese subjects (BMI≥ 30 kg/m² ).
4. Screening period, fasting LDL-C > 110 mg/dL (2.85 mmol/L).
5. Female or male subjects must be eligible for contraception during the study.
6. Normal renal function (calculate glomerular filtration rate using CKD-EPI equation≥ 80mL/min/1.73m² ).
7. Good general health.
8. No significant medical history, in good general health as assessed by the study during the Screening Period and no more than 28 days from the first dose.

Exclusion Criteria:

SAD

1. Special dietary requirements, not following a uniform diet.
2. Pregnant or nursing females or females who have pregnancy plans during the trial or within 3 months after the trial.
3. History of febrile illness or active infection within 7 days prior to first dose.
4. Positive urine drug screening results.
5. History of drug/substance abuse experiments within the past 5 years prior to the start, The baseline drug screening result is positive.

6. History of previous corrected QT interval (QTc) prolongation:

   1. Screening periods QTcF ≥ 450 ms.
   2. Family history of hypocalcaemia or long QT interval syndrome.
   3. Use of drugs causing QT/QTc prolongation.
   4. Investigator judgement of clinically significant abnormal ECG results.
7. Abnormal liver function: AST, ALT, ALP, GGT and TBIL>ULN.
8. Smoking or use of nicotine products within 3 months prior to screening and during the study period.
9. Use of other investigational drugs 40 days prior to enrolment or within at least 5 half-lives of drug use.
10. Positive screening results for infectious diseases during the screening period, include HIV, HBsAg, HBcAb, HCV antibody tests.
11. Any abnormal results of laboratory tests judged by the investigator to be clinically significant during the screening period.
12. Blood loss within 40 days prior to administration 50~500 mL, or loss of more than 500 mL of blood within 56 days prior to administration.
13. Drinking alcohol 48 hours before screening or during CRU period.
14. Prescription and over-the-counter use within 14 days or at least 5 half-lives prior to the baseline period, or use of any other substance that may affect CYP3A activity within 14 days or at least 5 half-lives before taking this study drug.
15. History of thyroid disease or clinically significant thyroid test abnormalities.
16. Allergy to thyroid medication.
17. Presence of any disease that may interfere with the absorption, distribution, metabolism or excretion of drugs, Including bile salt metabolism in the colon, such as gastrectomy, inflammatory bowel disease, etc.
18. According to the researcher's judgment, there are clinically significant diseases found, including but not limited to (gastrointestinal, kidney, liver, nervous, blood, endocrine, tumor, lung, immune, mental or cardiovascular diseases), researchers believe that participating in the study poses risks to participants.
19. Allergy to the investigational drug or any component of the investigational drug, allergy history and constitution.
20. Diseases or conditions with clinical significance that researchers believe may pose a risk to the safety of subjects or interfere with the conduct, progress, or completion of the study.
21. Abnormal thyroid function test during screening.
22. Screening or baseline cardiac troponin>ULN.

MAD

1. Special dietary requirements that cannot follow a unified diet.
2. Pregnant or lactating women who have a pregnancy plan during or within 3 months after the trial, female subjects tested positive for pregnancy during screening or baseline period.
3. Individuals with a history of febrile diseases or active infections within 7 days prior to the first administration of medication.
4. Positive urine drug screening results during screening or baseline period.
5. History of drug/drug abuse within 5 years prior to the start of the trial, or positive drug screening results during screening or baseline period.
6. Subjects who are receiving lipid-lowering treatment or have LDL-C>190 mg/dL and have a family history of coronary heart disease, arrhythmia, unexplained syncope, or cardiac arrest.

7. History of QTc extension in the past:

   1. Screening period QTcF ≥ 450 ms.
   2. Family history of hypocalcemia or long QT interval syndrome.
   3. Using drugs that cause QT/QTc prolongation.
   4. Abnormal results of ECG with clinical significance determined by researchers.
8. Abnormal liver function: AST, ALT, ALP, GGT and TBIL>ULN.
9. Screening for smoking or using nicotine products within the first 3 months and during the study period.
10. Use of other investigational drugs 40 days prior to enrolment or within at least 5 half-lives of drug use.
11. Positive screening results for infectious diseases during the screening period, include HIV, HBsAg, HBcAb, HCV antibody Tests.
12. Any abnormal results of laboratory tests judged by the investigator to be clinically significant during the screening period.
13. Blood loss within 40 days prior to administration 50~500 mL, or loss of more than 500 mL of blood within 56 days prior to administration.
14. Men and women who consumed more than 1 unit per day prior to screening, [1 unit = 150 ml of wine, 360 ml of beer or 45 ml of 40% alcohol], drinking alcohol 48 hours before administration and during CRU.
15. Prescription and over-the-counter use within 14 days or at least 5 half-lives prior to the baseline period, or use of any drug or other substance that may affect CYP3A activity within 14 days or at least 5 half-lives before taking this study drug.
16. History of thyroid disease or clinically significant thyroid test abnormalities.
17. Allergy to thyroid medication.
18. Presence of any disease that may interfere with the absorption, distribution, metabolism or excretion of drugs, Including bile salt metabolism in the colon, such as gastrectomy, inflammatory bowel disease, etc.
19. According to the researcher's judgment, there are clinically significant diseases found, including but not limited to (gastrointestinal, kidney, liver, nervous, blood, endocrine, tumor, lung, immune, mental or cardiovascular diseases), researchers believe that participating in the study poses risks to participants.
20. Allergy to the investigational drug or any component of the investigational drug, Allergy history and constitution.
21. Diseases or conditions with clinical significance that researchers believe may pose a risk to the safety of subjects or interfere with the conduct, progress, or completion of the study.
22. Abnormal thyroid function test during screening.
23. Screening or baseline cardiac troponin>ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1: 0.2 mg CS060380; Eight healthy subjects were randomly assigned to take 0.2 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach).	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A2: 1 mg CS060380; Eight healthy subjects were randomly assigned to take 1 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach).	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A3: 2 mg CS060380; Eight healthy subjects were randomly assigned to take 2 mg of CS060380 or placebo on day 1, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach). Followed by a 10 day washout period, subjects in fed state will receive the same single oral dose of CS060380 2mg or placebo on day 11.	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A4: 5 mg CS060380; Eight healthy subjects were randomly assigned to take 5 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach).	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort A5: 10 mg CS060380; Eight healthy subjects were randomly assigned to take 10 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach).	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort B1: 1 mg CS060380; Elevated LDL-C subjects were randomly assigned to take 1 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort B2: 2 mg CS060380; Elevated LDL-C subjects were randomly assigned to take 2 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort C1: 0.25 mg CS060380; Elevated LDL-C subjects were randomly assigned to take 0.25 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort C2: 0.5 mg CS060380; Elevated LDL-C subjects were randomly assigned to take 0.5 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort C3: 0.75 mg CS060380; Elevated LDL-C subjects were randomly assigned to take 0.75 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort D1: 0.1 mg CS060380; Elevated LDL-C subjects were randomly assigned to take 0.1 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort D2: 0.15 mg CS060380; Elevated LDL-C subjects were randomly assigned to take 0.15 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.	Drug: CS060380; Tablets administered orally; Other Names: Placebo
Experimental: Cohort D3: 0.2 mg CS060380; Elevated LDL-C subjects were randomly assigned to take 0.2 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.	Drug: CS060380; Tablets administered orally; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE	occurrence rate of AEs	Day1 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single-Dose Pharmacokinetic (PK) Parameter (AUC0-∞)	AUC from time zero to infinity	Day 1, day 2, day3, day4.
Single-Dose Pharmacokinetic (PK) Parameter (AUC0-last)	AUC from time zero to the last quantifiable concentration	Day 1, day 2, day3, day4.
Single-Dose Pharmacokinetic (PK) Parameter (Cmax)	Maximum observed plasma concentration	Day 1, day 2, day3, day4.
Single-Dose Pharmacokinetic (PK) Parameter (Tmax)	Time to the maximum observed plasma concentration	Day 1, day 2, day3, day4.
Single-Dose Pharmacokinetic (PK) Parameter (T1/2)	Elimination half-life	Day 1, day 2, day3, day4.
Single-Dose Pharmacokinetic (PK) Parameter (CL/F)	Apparent total plasma clearance	Day 1, day 2, day3, day4.
Single-Dose Pharmacokinetic (PK) Parameter (Kel)	Elimination rate constant	Day 1, day 2, day3, day4.
Single-Dose Pharmacokinetic (PK) Parameter (MRT)	Mean residence time	Day 1, day 2, day3, day4.
Single-Dose Pharmacokinetic (PK) Parameter (Vz/F)	Apparent volume of distribution	Day 1, day 2, day3, day4.
Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_max)	Maximum concentration during a dosing interval	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_min)	Minimum concentration during a dosing interval	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Multiple-Dose Pharmacokinetic (PK) Parameter (AUCtau)	AUC over one dosing interval	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Multiple-Dose Pharmacokinetic (PK) Parameter (Tmax)	Tmax	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Multiple-Dose Pharmacokinetic (PK) Parameter (T1/2)	T1/2	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Multiple-Dose Pharmacokinetic (PK) Parameter (CL/F)	CL/F	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Multiple-Dose Pharmacokinetic (PK) Parameter (DF)	Degree of fluctuation	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_av)	Mean plasma concentration during a dosing interval	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.
Multiple-Dose Pharmacokinetic (PK) Parameter (Rac)	Accumulation factor	Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic (PD) Characteristics (Fasting serum LDL-C)	PD Characteristics of Multiple Oral Doses of CS060380 in Subjects with Elevated LDL-C	Day 1, day 3, day 5, day 7, day 14, day 15, day 17.
Pharmacodynamic(PD) Characteristics (HDL-C)	High-density lipoprotein cholesterol.	Day 1, day 3, day 5, day 7, day 14, day 15, day 17.
Pharmacodynamic (PD) Characteristics (TG)	Triglyceride.	Day 1, day 3, day 5, day 7, day 14, day 15, day 17.
Pharmacodynamic (PD) Characteristics (TC)	Total cholesterol.	Day 1, day 3, day 5, day 7, day 14, day 15, day 17.
Pharmacodynamic (PD) Characteristics (Apo B)	Apolipoprotein B.	Day 1, day 3, day 5, day 7, day 14, day 15, day 17.
Pharmacodynamic (PD) Characteristics (SHBG)	Sex hormone binding globulin.	Day 1, day 3, day 5, day 7, day 14, day 15, day 17.
Thyroid function indicators (Total serum T3)	Total serum T3	Day 3, day 7, day 10 , day 15, day 17.
Thyroid function indicators (T3)	Disassociate T3	Day 3, day 7, day 10 , day 15, day 17.
Thyroid function indicators (T4)	Thyroxine T4.	Day 3, day 7, day 10 , day 15, day 17.
Thyroid function indicators (disassociate T4)	Disassociate T4.	Day 3, day 7, day 10 , day 15, day 17.
Thyroid function indicators (TSH)	Thyroid stimulating hormone.	Day 3, day 7, day 10 , day 15, day 17.
Drug concentration (QTcF)	Orrected QT interval by Fridericia formula.	Day 1, day 2, day 3.

Collaborators and Investigators

• Sponsor: Cascade Pharmaceuticals, Inc
• Investigators: Principal Investigator: Yun Liu, Shanghai Xuhui Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2024
• Primary Completion (Actual): May 9, 2025
• Study Completion (Actual): May 21, 2025

Study Registration Dates

• First Submitted: August 19, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: CS060380-FIH-CN-I-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No